This renewal application seeks support for the infrastructure of the Multiethnic Cohort (MEC) Study, which was established in Hawaii and southern California in 1993-1996 to study risk factors for cancer and other chronic diseases. The study was designed to take advantage of the ethnic and cultural diversity of the two geographic areas, as well as the expertise of the investigators in nutrition, ethnic/racial studies, and genetics. It is the most ethnically diverse cancer cohort in existence. It achieves high cost-efficiency by supplementing active follow-up information with computerized linkages to SEER, vital statistics, hospital-discharge diagnoses, medical claim data, electronic medical records and geospatial information. At baseline, the cohort included information on 215,000 men and women, comprised almost entirely of five ethnic/racial populations: Caucasians, Japanese Americans, Native Hawaiians, African Americans, and Latinos. The resource was later expanded to include a prospective biorepository of blood and urine specimens from ~70,000 of the participants. Leadership of the MEC entails a highly interactive, team approach; and the investigators have amply demonstrated their willingness to share data/samples, and to participate actively in consortia. This application describes our aims over the next 5 years for maintaining and enhancing the infrastructure of the MEC, as well as plans for methodological research. Research accomplishments include significant contributions to understanding both genetic and environmental risk factors for cancer. Over 280 papers describing our findings have been published during the current grant cycle. In addition, over the last 20 years, 98 research grants have been built around the MEC, and more than 75 students and postdoctoral fellows have been trained on the study. This grant renewal will make possible the continuation of a well-integrated program of research aimed at evaluating environmental and genetic risk factors for cancer and other common chronic diseases, taking advantage of new approaches, such as genomics, microbiomics, adductomics and metabolomics. The MEC will allow the testing of innovative research hypotheses aimed at ensuring that progress in prevention applies to major US ethnic/racial minorities.